MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer

BMC Cancer

Xiuwen Zhang¹  Yi Shao²  Mengjie Li³  Mingming Wei⁴  Hongli Pan⁵  Yaguang Fan⁵  Zhenhua Pan⁵  Fengjie Guo⁵  Xinxin Du⁵  Yang Li⁵  Lingling Zu⁵  Xuebing Li⁵  Qinghua Zhou⁶  Fanrong Meng⁷ 

[1] Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China;Department of Thoracic Surgery, Yizheng People’s Hospital, Yangzhou, Jiangsu Province, China;Department of Oncology, Tianjin Medical University General Hospital, Tianjin, China;Sichuan Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China;The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, China;Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China;Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China;Sichuan Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China;Tianjin Prenatal Diagnostic Center, Obstetrics and Gynecology Department, Tianjin Medical University General Hospital, Tianjin, China;

关键词: NSCLC;    miR-1915-3p;    Invasion;    Migration;    SET;   

DOI  :  10.1186/s12885-021-08961-8

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC.MethodsThe expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP).ResultsmiR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3′untranslated region (3′UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What’s more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4.ConclusionsThese findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.

【 授权许可】

CC BY